2,2-Difluoro-13,14-dihydro-PGE1 analogs

Abstract

2,2-Difluoro prostaglandin E, F.sub.α, F.sub.β, A, and B analogs are disclosed with intermediates and with processes for making them. These compounds differ from the prostaglandins in that they have two fluoro atoms at the C-2 position in place of the two hydrogen atoms at C-2 in the prostaglandins. These compounds are useful for a variety of pharmacological purposes, including antiulcer, inhibition of platelet aggregation, increase in nasal patency, labor induction at term, and wound healing.

I claim: 
     
       1. A compound of the formula ##STR1##or a mixture comprising that compound and the enantiomer thereof, WHEREIN G IS 2 TO 4, INCLUSIVE; Wherein M 1  is ##STR2##wherein R 7  and R 8  are hydrogen or methyl, with the proviso that one of R 7  or R 8  is methyl only when the other is hydrogen;   Wherein m is 2 to 4, inclusive;   Wherein R 1  is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, 2, or 3 chloro, alkyl of one to 4 carbon atoms, inclusive, or a pharmacologically acceptable cation, ##STR3## WHEREIN R 5  is hydrogen, methyl, or fluoro with the proviso that R 5  is fluoro only when R 7  and R 8  are both hydrogen, with the proviso that R 5  is methyl only when R 7  and R 8  are both hydrogen, and with the proviso that R 5  is hydrogen only when either one of R 7  and R 8  is methyl.   
     
     
       2. A compound according to claim 1, wherein M 1  is ##STR4## 
     
     
       3. A compound according to claim 2, wherein g is 2. 
     
     
       4. A compound according to claim 3, wherein m is 3. 
     
     
       5. A compound according to claim 4, wherein R 7  is methyl. 
     
     
       6. 2,2-Difluoro-15-methyl-13,14-dihydro-PGE 1 , a compound according to claim 5, wherein R 1  is hydrogen. 
     
     
       7. 2,2-Difluoro-15-methyl-13,14-dihydro-PGE 1 , methyl ester, a compound according to claim 5, wherein R 1  is methyl. 
     
     
       8. A compound according to claim 4, wherein R 8  is methyl. 
     
     
       9. 2,2-Difluoro-13,14-dihydro-PGE 1 , 15-methyl ether, a compound according to claim 8, wherein R 1  is hydrogen. 
     
     
       10. 2,2-Difluoro-13,14-dihydro-PGE 1 , 15-methyl ether, methyl ester, a compound according to claim 8, wherein R 1  is methyl. 
     
     
       11. A compound according to claim 4, wherein R 7  and R 8  are hydrogen. 
     
     
       12. A compound according to claim 11, wherein R 5  is methyl. 
     
     
       13. 2,2-Difluoro-16,16-dimethyl-13,14-dihydro-PGE 1 , methyl ester, a compound according to claim 12, wherein R 1  is methyl. 
     
     
       14. 2,2-Difluoro-16,16-dimethyl-13,14-dihydro-PGE 1 , methyl ester, a compound according to claim 12, wherein R 1  is methyl. 
     
     
       15. A compound according to claim 11, wherein R 5  is fluoro. 
     
     
       16. 2,2,16,16-Tetrafluoro-13,14-dihydro-PGE 1 , a compound according to claim 15, wherein R 1  is hydrogen. 
     
     
       17. 2,2,16,16-Tetrafluoro-13,14-dihydro-PGE 1 , methyl ester, a compound according to claim 15, wherein R 1  is methyl. 
     
     
       18. The compound according to claim 1, wherein M 1  is